Cellular Mechanisms of Brain Remodelling and Preservation in Fetal Development Under Altered Intrauterine Conditions

Research in developmental neurobiology continues to unravel the vulnerability of the fetal brain to altered intrauterine environments. Prenatal conditions such as intrauterine growth restriction (IUGR), placental insufficiency, hypoxia, inflammation, and maternal metabolic stress can disrupt tightly regulated pathways governing brain development, with lifelong consequences for neurological and psychiatric health. Recent years have seen significant advances in our ability to characterize how these adverse conditions affect cellular populations—ranging from neural progenitors to maturing neurons and glia—at both molecular and functional levels. Notably, mechanistic studies reveal that intrauterine adversity can trigger epigenetic modifications, disrupt growth factor signaling, and foster a deleterious imbalance in neuroinflammatory and metabolic pathways. Despite these gains, there remains a crucial need to understand how early cellular and molecular disturbances map onto later structural and functional phenotypes, and why some brains demonstrate resilience while others succumb to dysfunction.Current debates surround the relative contributions of direct fetal programming versus indirect influences, such as maternal physiology and placental health, in shaping brain development. While complementary in vitro and in vivo models have shed light on foundational mechanisms, inconsistencies in methodologies and a lack of standardized outcome measures continue to hinder integrative, translational understanding. Furthermore, longitudinal studies that span from prenatal disruption through postnatal neurodevelopmental outcomes are still limited, leaving crucial questions around causality and temporal dynamics unanswered. Importantly, there is growing recognition of the potential to rescue or preserve brain development through targeted interventions—including bioactive compounds with neurotrophic, metabolic, or anti-inflammatory properties—but systematic evaluation of their efficacy and mechanisms remains in its infancy.This Research Topic aims to advance comprehensive knowledge of how adverse intrauterine environments influence fetal brain development, focusing on unraveling the links between underlying molecular mechanisms and later neurological outcomes. By integrating evidence from complementary cell culture systems, organoids, and animal models, the goal is to map the sequential changes that occur from early molecular disruptions through to structural remodeling, altered electrophysiological properties, and behavioral phenotypes. In addition, the topic seeks to evaluate candidate interventions capable of mitigating or reversing damaging patterns of brain reprogramming. A special emphasis is placed on submissions that not only dissect mechanistic underpinnings but also employ multidisciplinary approaches to assess both cellular endpoints and higher-order neurodevelopmental functions, thereby promoting insights with robust translational relevance.The scope of this Research Topic includes original research, method development, review articles, and protocols that focus on mechanistic and interventional studies of prenatal brain development in the context of intrauterine stress. It is limited to models examining cellular, molecular, and functional brain outcomes associated specifically with fetal exposure to adverse intrauterine conditions. To facilitate a rigorous and unified body of knowledge, we particularly encourage studies that enhance methodological standardization and reproducibility.To gather further insights in this area, we welcome articles addressing, but not limited to, the following themes:• Mechanisms governing neural progenitor behavior and fate specification under intrauterine stress• Disruptions in differentiation, maturation, and connectivity of neuronal and glial populations• Structural, electrophysiological, and behavioral phenotypes linked to prenatal adversity• Evaluation of neuroprotective, metabolic, and anti-inflammatory interventions and their mechanisms of action• Development, validation, and harmonization of methodologies for neurodevelopmental assessment, including neurosphere/organoid assays and in vivo phenotyping• Innovations to maximize rigor, reproducibility, and translational applicability in studies on perinatal brain development Topic editors: Míriam Illa, Suzanne Lee Miller, Luis Federico Batiz, Sebastian E Illanes, Ignacio Valenzuela Source: https://www.frontiersin.org/research-topics/78860/cellular-mechanisms-of-brain-remodelling-and-preservation-in-fetal-development-under-altered-intrauterine-conditions